Functional analysis of Ccr3 associated with narcolepsy

2017 Fiscal Year Final Research Report

• Project/Area Number: 26870117
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology); Psychiatric science
• Research Institution: The University of Tokyo
• Principal Investigator: Toyoda Hiromi 東京大学, 大学院医学系研究科(医学部), 客員研究員 (90637448)
• Research Collaborator: HONDA Yoshiko ; KODAMA Tohru ; TANAKA Susumu ; MIYAGAWA Taku
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: ナルコレプシー / 睡眠 / Ccr3 / ケモカイン受容体 / オレキシン細胞

Outline of Final Research Achievements

Narcolepsy is caused by the loss of hypocretin (Hcrt) neurons. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. I previously reported CCR3 as a novel susceptibility gene for narcolepsy. This study investigated sleep-wake patterns of Ccr3 KO mice to understand the role of CCR3 in the development of narcolepsy.
Ccr3 KO mice exhibited fragmented sleep patterns in the resting phase. Intraperitoneal injection of LPS promoted wakefulness and suppressed both REM and NREM sleep in the resting phase in both Ccr3 KO and WT mice. These LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice.
We propose that impaired function of Ccr3 causes fragmented sleep that can contribute to vulnerability to developing narcolepsy in an inflammatory context induced by environmental triggers.

Free Research Field

遺伝学